- Email: [email protected]
Robotic Laparoendoscopic Single-site Transumbilical Partial Nephrectomy: Functional and Oncologic Outcomes at 2 Years
Laparoscopy and Robotics Robotic Laparoendoscopic Single-site Transumbilical Partial Nephrectomy: Functional and Oncologic Outcomes at 2 Years Albert Tiu, Tae Y. Shin, Kwang H. Kim, Sey K. Lim, Woong K. Han, and Koon H. Rha OBJECTIVE MATERIALS AND METHODS
RESULTS
CONCLUSION
To assess the functional and oncologic outcomes of robotic laparoendoscopic single site surgery (LESS) partial nephrectomy with a minimum of 2-year follow-up. Thirty-nine consecutive patients who had undergone robotic LESS partial nephrectomy were identified with a minimum of 2-year follow-up. Perioperative data were recorded along with functional and oncologic outcomes. Patient’s estimated glomerular filtration rate was determined using the Modification of Diet in Renal Disease formula. A univariate analysis was performed using independent samples t test. Data are presented as medians with interquartile range and counts or frequencies with percentages or proportion. The median age was 51 (45, 59). The median resected tumor size was 3 cm (2, 3.7), and the median operative time was 185 minutes (135, 237). The median estimated blood loss was 150 mL (70, 150), and the median warm ischemia time was 25 minutes (17, 35). The estimated glomerular filtration rate did not change significantly at 24 month follow-up with a mean decrease of 6.4 mL/minute/1.73 m2 (7.5%, P ¼ .22). Renal cell carcinoma was confirmed in 33 patients (85%) with tumor stage pT1a in 26 patients (78%). There was 1 patient with a positive surgical margin. At a median follow-up of 26 months (24, 32), there was no local recurrence and only 1 distant recurrence was detected. This study appears to be the first to report on intermediate term functional and oncologic outcomes after robotic LESS partial nephrectomy. It has shown comparable results with other minimal invasive surgical options. UROLOGY 82: 595e599, 2013. 2013 Elsevier Inc.
N
ephron sparing surgery is now considered as the standard treatment for small renal tumors whenever it is technically feasible, owing to the advantage of preserving renal function and with long-term oncologic results equivalent to that of radical nephrectomy.1 Laparoscopic partial nephrectomy has emerged as a viable alternative to open partial nephrectomy for clinical stage T1 renal tumor, with similar oncologic and functional outcomes and also convalescence benefits.2 Since the first laparoscopic nephrectomy reported by Clayman et al in 1990, there have been major breakthroughs in laparoscopic surgery of the urinary tract.3 Financial Disclosure: The authors declare that they have no relevant financial interests. Funding Support: This study was supported by a faculty research grant of Yonsei University College of Medicine for 2012 (6-2012-0181). From the Urological Society of Australia and New Zealand, Edgecliff, New South Wales, Australia; the Department of Urology, University of Miami, Miller School of Medicine, Miami, FL; and the Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea Reprint requests: Koon H. Rha, M.D., Ph.D., Department of Urology, Urological Science Institute, Yonsei University College of Medicine, 250 Seongsanno, Seodaemungu, Seoul 120-752, Republic of Korea. E-mail: [email protected] Submitted: January 23, 2013, accepted (with revisions): May 5, 2013
ª 2013 Elsevier Inc. All Rights Reserved
With technological advancements and improvements in equipment, urologists have gained significant momentum in further minimizing the surgical approach with the development of laparoendoscopic single site surgery (LESS). LESS involves accessing the abdominal cavity through a readily concealed 3 cm-4 cm incision at the umbilicus, hence might minimize patient discomfort, shorten convalescence, and improve cosmesis.4 However, challenges encountered with LESS include difficulty with using the novel bent and articulating instruments in close proximity to one another, resulting in loss of triangulation and instrument clashing.5 The introduction of robotic technology has provided some attractive features such as magnified 3 dimensional vision, articulating instruments, scaling of movement and tremor filtration, fourth robotic arm assistance, and TilePro, a live intraoperative ultrasound platform. Consequently, these features have reduced the crowding of instruments, enabled better precision with tumor resection and renal reconstruction. Nevertheless, there is still paucity of relevant studies of robotic LESS partial nephrectomy on its intermediate term clinical outcomes as it is a relatively new approach. 0090-4295/13/$36.00 http://dx.doi.org/10.1016/j.urology.2013.05.010
595
In this study, we analyzed the 2-year functional and oncologic outcomes of robotic LESS partial nephrectomy using a homemade single-port device.
MATERIALS AND METHODS Forty-four consecutive patients who had undergone robotic LESS partial nephrectomy were identified initially from our institutional review board approved computerized database between May 2009 and March 2010. Five patients who had other concurrent procedures performed were excluded. The remaining 39 patients who had a minimum of 2 years follow-up were analyzed. Our operative technique of robotic LESS partial nephrectomy using homemade single port device has been detailed previously.6 The patient was placed in the conventional flank position at approximately 45 with the ipsilateral side elevated. A 4-cm-long incision was made down to the peritoneum over the umbilicus, followed by installment of an Alexis wound retractor (Applied Medical, Rancho Santa Margarita, CA). A size 7 surgical glove was then applied over the external side of the Alexis wound retractor and a homemade single port was established by inserting two 12-mm trocars and two 8-mm trocars through the fingers of a surgical glove and securing it to the port (Fig. 1A). The camera was inserted through the 12-mm port of the homemade single port, the robot arms were inserted through the 8-mm robotic port, and the second 12-mm port was used for insufflation and as an assistant port. The fourth robotic arm is not routinely used in our patients. For right-sided cases, an addition 5-mm port is inserted in the subxiphoid area for liver retraction. The robot was then docked over the patient’s shoulder, with the camera oriented in line with the kidney (Fig. 1B). The specimen is retrieved in the 10 mm endocatch bag and removed through the umbilical single port site. All the patients in the present study were completed with da Vinci S surgical system (Intuitive Surgical, Sunnyvale, CA). Intraoperative ultrasound with TilePro projection onto the console screen was used to confirm the margins of the mass and guide scoring the renal capsule with electrocautery. Temporary occlusion of the renal artery and vein was performed by the placement of laparoscopic bulldog clamps by the assistant. The tumor was then excised using the Endowrist monopolar scissors (Intuitive Surgical, Sunnyvale, CA). Frozen section biopsy specimens of the tumor base were taken. The renal defect was reconstructed using the sliding clip technique. At our institution, patient routine follow-up consisted of history and physical examination, and serum creatinine at 1, 3, 6, and 12 months, and then annually thereafter. Radiographic evaluation comprised computerized tomography or magnetic resonance imaging of the chest and abdomen at 6 months, and then annually after robotic LESS partial nephrectomy. Nephrometry score was used to characterize the renal tumor anatomy by using the R.E.N.A.L system (Radius; exophytic or endophytic, nearness to the renal sinus fat or collecting system, anterior or posterior position, and location).7 Patient’s estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Disease formula.8 Complications were graded according to the Clavien classification.9
Statistical Analysis A univariate analysis was performed using independent samples t test. Data were presented as medians with interquartile range
596
Figure 1. (A) Schematic drawing of homemade device with ports inserted into the digits of the surgical glove. (B) Schematic drawing of the homemade device after docking of robot, with the assistant port shown in black arrow. (Color version available online.) and counts or frequencies were expressed as percentages. All statistical analyses were performed using the SPSS software package (IBM Corp., Somers, NY) and a P value <.05 was considered statistical significant.
RESULTS Thirty-nine consecutive patients with a minimum of 2 years follow-up were available for evaluation. There were 15 patients with right-sided renal tumor and 24 patients with left-sided renal tumor. All patients were completed with a homemade single port device except for 1 patient who was converted to mini incision partial nephrectomy owing to difficulty in accessing the endophytic tumor located at the right posterior upper pole with the robotic arm. Demographic data are outlined in Table 1. The median age of patient was 51 (45, 59), with 25 men and 14 women, respectively. The overall mean and median nephrometry scores were 6.7 and 7, respectively (range 4-11; interquartile range 6, 8). The clinical results are summarized in Table 2. The median operative time was 185 minutes (135, 237), with median warm ischemia time of 25 minutes (17, 35). The median estimated blood loss was 150 mL (70, 150), and the median
UROLOGY 82 (3), 2013
Table 1. Demographic data
Table 2. Clinical results
Median age (IQR) 51 (45, 59) Sex, male 25 Median BMI (IQR) 23.2 (21.9, 25.2) Comorbidities Diabetes 3 (7%) Hypertension 9 (23%) ASA 1 and 2 37 (95%) 3 and 4 2 (5%) Median tumor size, cm (IQR) 3 (2, 3.7) Mean/median nephrometry 6.7/7 (6, 8) score (IQR) Low (4 to 6) 14 (36%) Moderate (7 to 9) 20 (51%) High (10 to 12) 5 (13%) Nephrometry score components R-score (maximal diameter, cm) 4 (1 point) 29 >4 but <7 (2 points) 9 7 (3 points) 1 E-score (exophicity) 50% (1 point) 25 50% (2 points) 14 Entirely endophytic (3 points) 0 N-score (nearness of tumor to sinus mm) 7 (1 point) 4 >4 but <7 (2 points) 30 4 (3 points) 5 A/P designation (anterior vs posterior) Anterior 26 Posterior 13 L-score (polar line location) Entirely above upper or below 5 lower polar line (1 point) Tumor crosses polar line 28 (2 points) >50% of tumor cross polar line 6 or is entirely within the polar lines (3 points)
Median operative time, min (IQR) Median warm ischemia time, min (IQR) Median estimated blood loss, mL (IQR) Conversion to open partial nephrectomy Histology subtypes Conventional RCC Other RCC subtype Benign Positive final margin Pathologic stage pT1a pT1b pT2 or higher Median baseline GFR, mL/min/ 1.73 m2 (IQR) Median GFR at 1 mo, mL/min/ 1.73 m2 (IQR) Median GFR at 3 mo, mL/min/ 1.73 m2 (IQR) Median GFR at 6 mo, mL/min/ 1.73 m2 (IQR) Median GFR at 12 mo, mL/min/ 1.73 m2 (IQR) Mean GFR at 24 mo, mL/min/ 1.73 m2 (IQR) % Change mean GFR at 24 mo Median follow-up, mo (IQR) Complications Grade 2 (hemorrhage requiring transfusion) Grade 3 (urine leak requiring stent)
ASA, American Society of Anesthesiologists; BMI, body mass index; IQR, interquartile range.
resected tumor size was 3 cm (2, 3.7). The final histologic analysis showed renal cell carcinoma in 33 patients (85%), of which, 26 patients (79%) had Fuhrman grade I/II. There were 26 patients (79%) with pathologic stage pT1a, 6 patients (18%) with pT1b, and 1 patient (3%) with pT2. All surgical margins were pathologically negative except for 1 patient, with a positive margin rate of 3%. All patients except for 2 reported a preoperative eGFR of more than 60 mL/minute/1.73 m2. The eGFR did not change significantly at the 24 month follow-up with a mean decrease of 6.4 mL/minute/1.73 m2 (7.5%, P ¼ .22). The median follow-up was 26 months (24, 32) and no patients required dialysis. There were 2 intraoperative complications; 1 patient had renal vein injury, which was successfully controlled with intracorporeal suturing, whereas the other patient had ureteric injury and required insertion of a ureteric stent. Postoperative complications occurred in 6 patients (15%), of which 5 required blood transfusion (DindoClavien grade 2) and 1 patient developed urine leakage UROLOGY 82 (3), 2013
185 (135, 237) 25 (17, 35) 150 (70, 150) 1 (2.5%) 28 5 6 1 26 6 1 85.4
(72%) (13%) (15%) (3%) (79%) (18%) (3%) (77.7, 98.1)
78 (68.7, 90) 74.6 (68.2, 88) 75.6 (68.8, 88) 78 (70.3, 89) 79 (71, 90) 7.5% (P ¼ .22) 26 (24, 32) 5 (13%) 1 (2.5%)
GFR, glomerular filtration rate; RCC, renal cell carcinoma; other abbreviation as in Table 1.
(Dindo-Clavien grade 3), which was managed with a ureteric stent. There was only 1 patient (3%) with distant pulmonary metastasis at 18 months who had a high-grade pT1b papillary renal cell carcinoma with negative margin. There were no patients who experienced local recurrence, death from cancer, or other causes.
COMMENT Urology has increasingly become a technology-driven specialty, where minimal invasive surgery is now part of the standard armory. Robotic LESS partial nephrectomy represents an attractive and minimally invasive treatment option for patients with small renal tumors. Our initial experiences with conventional LESS and robotic LESS in urology were reported in collaboration with the largest worldwide multi-institutional study.10 To our knowledge, the present study is the first that directly assesses the intermediate term functional and oncologic outcomes of robotic LESS partial nephrectomy. Analyzing the renal function outcomes, the eGFR did not change significantly at the follow-up of 24 months with a mean decrease of 6.4 mL/minute/1.73 m2 (7.5%, P ¼ .22) and is within 597
Table 3. Oncologic outcomes of selected series of partial nephrectomy for renal masses Study Lerner et al25 Hafez et al26 Gill et al2 Gill et al2 Lane and Gill27 Benway et al21 Present study
Approach
Patient No.
Median Follow-up (mo)
Median Tumor Size (cm)
Local Recurrence %
Distant Recurrence %
Open Open Open Laparoscopic Laparoscopic Robotic Robotic LESS
185 485 1029 771 58 183 39
44 (Mean) 47 (Mean) 34 15 68 16 26
4.1 2.7 3.5 2.9 2.9 2.87 3
5.9 3.2 1.5 2.7 2.7 0 0
17 5.8 2.1 0.9 0 0 3
LESS, laparoendoscopic single site surgery.
the range (4.5-8.0 mL/minute/1.73 m2) of those reported series.11-14 The mean GFR decrease was the greatest at 3 months and then recovered progressively toward the preoperative level. Detailed description of eGFR changes over time is reported in Table 2. Song et al have shown that the recovery of renal function after partial nephrectomy is impacted by patient age, comorbidities, and baseline renal function, along with the amount and depth of parenchyma excised.15 Interestingly, these investigators have reported warm ischemia times to have no impact on renal function. One possible explanation for this observation in the aforementioned study is that fewer patients had baseline compromise (ie pre-existing comorbidities and chronic kidney disease). Nevertheless, a large body of published data has shown that warm ischemia time is a significant predictor of ultimate renal function.16-18 Our median warm ischemia time of 25 minutes is comparable with other published robotic series ranging from 21 to 31 minutes.13,19,20 One patient had a positive surgical margin, despite the fact that the intraoperative frozen section of the resection margin was negative. This 62-year-old woman had a 2.2 cm Fuhrman 3 clear cell renal cell carcinoma. Her subsequent follow-up serial radiological studies have ruled out any evidence of local or distant recurrence. Our positive surgical margin rate of 3% is consistent with previous robotic and laparoscopic series.21,22 In a retrospective study, Benway et al reported a positive margin rate of 2.7% of the 183 patients who underwent robotic partial nephrectomy at 4 centers.21 Likewise, in a multiinstitutional survey of 17 academic centers in the United States and Europe, there were 21 identified cases of positive surgical margins in an overall series of 855 laparoscopic partial nephrectomy (2.4%).22 Moreover, the presence of positive resection margin has been shown to have no adverse effect on the overall oncologic outcome. A large study by 2 institutions in the United States had shown that positive surgical margins in partial nephrectomy specimens do not appear to increase the long-term risk of local recurrence or metastatic progression, and that patients with a positive surgical margin can be monitored closely without compromising on long-term disease-free survival.23 Another multi-institutional European retrospective study had revealed that the indication and tumor location, rather than margin status, were
598
significant predictors of local recurrence with a mean follow-up of 37 months.24 No single local recurrence was detected in the present study; however, 1 patient developed pulmonary metastasis at 18 months follow-up. This was a 74-year-old man who had a 4.3 cm papillary type renal cell carcinoma with negative resection margin. He was referred to a medical oncologist and was commenced on sorafenib treatment (tyrosine kinase inhibitor) for his metastatic renal cell carcinoma. He was due to have subsequent radiographic imaging after the treatment course. Our 0% local recurrence and 3% distal recurrence rates are comparable with some of the major series in the published reports listed in Table 3. There was no patient from the present study who died from cancer specific or other causes. It is noteworthy that the cohort in this study was generally not obese with a mean body mass index of 23.2 (21.9, 25.2). As such, the result from this study might not be extrapolated into other countries where obesity is an issue. It is well established that obese patients are more likely to have multiple medical comorbidities, including hypertension and diabetes. Naeem et al had recently reported that robotic partial nephrectomy in obese patients resulted in higher estimated blood loss and a trend toward greater operative time and warm ischemia time.28 We recognize some of the limitations in the present study. The main one is the retrospective nature of the analysis, albeit our data were collected prospectively into a computerized database. Another limitation is the relatively small sample size. It is likely that larger prospective comparative studies will appear as experience with this new and emerging technique increases in the future and the learning curve is overcome. Furthermore, the use of an additional 5-mm subxiphoid liver retraction port for right-sided renal tumors was a deviation of the strict philosophy of LESS surgery; however, this seems to have become an accepted practice.29 Nevertheless, it must be acknowledged that the main disadvantage with our current technique is the fragility of the homemade single port access device, where accidental laceration of the glove during insertion of robotic instruments could have caused air leakage. There was 1 patient who required port-glove replacement because of ongoing air leak intraoperatively. Although several commercially
UROLOGY 82 (3), 2013
available single port access devices have been reported in published reports, it is inevitable that more research is required for the development and design of an ideal robotic platform.30
CONCLUSION This study appears to be the first to report on functional and oncologic outcomes after robotic LESS partial nephrectomy in the intermediate term. It has shown comparable results with other minimal invasive surgical options for the management of renal parenchymal tumor. However, there is potential in the future for longer term follow-up analysis, extending to larger study size across multi-institutions. Finally significant improvements are required to address the current challenge of robotic LESS surgery before this technique might be considered as the standard of care. References 1. Campbell SC, Novick AC, Belldegrun A, et al. Guideline for management of the clinical T1 renal mass. J Urol. 2009;182: 1271-1279. 2. Gill IS, Kavoussi LR, Lane BR, et al. Comparison of 1,800 laparoscopic and open partial nephrectomies for single renal tumors. J Urol. 2007;178:41-46. 3. Clayman RV, Kavoussi LR, Soper NJ, et al. Laparoscopic nephrectomy: initial case report. J Urol. 1991;146:278-282. 4. Gettman MT, Box G, Averch T, et al. Concensus statement on natural orifice transluminal endoscopic surgery and single-incision laparoscopic surgery: heralding a new era in urology? Eur Urol. 2008;53:1117-1120. 5. Autorino R, Kaouk JH, Stolzenburg JU, et al. Current status and future directions of robotic single-site surgery: a systematic review. Eur Urol. 2013;63:266-280. 6. Jeon HG, Jeong W, Oh CK, et al. Initial experience with 50 laparoendoscopic single site surgeries using a homemade, single port device at a single center. J Urol. 2010;183:1866-1871. 7. Kutikov A, Uzzo RG. The R.E.N.A.L. nephrometry score: a comprehensive standardized system for quantitating renal tumor size, location and depth. J Urol. 2009;182:844-853. 8. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461-470. 9. Dindo D, Demartines N, Clavien PA. Classification of surgical complications. Ann Surg. 2004;240:205-213. 10. Kaouk JH, Autorino R, Kim FJ, et al. Laparoendocopic single-site surgery in urology: worldwide multi-institutional analysis of 1076 cases. Eur Urol. 2011;60:998-1005. 11. Rogers CG, Singh A, Blatt AM, et al. Robotic partial nephrectomy for renal hilar tumours: a multiinstitutional analysis. J Urol. 2008; 180:2353-2356.
UROLOGY 82 (3), 2013
12. Gong Y, Du C, Josephson DY, et al. Four-arm robotic partial nephrectomy for complex renal cell carcinoma. World J Urol. 2010; 28:111-115. 13. Rogers CG, Singh A, Blatt AM, et al. Robotic partial nephrectomy for complex renal tumours: surgical technique. Eur Urol. 2008;53: 514-523. 14. Scoll BJ, Uzzo RG, Chen D, et al. Robot-assisted partial nephrectomy: a large single-institutional experience. Urology. 2010;75: 1328-1334. 15. Song C, Park S, Jeong IG, et al. Followup of unilateral renal function after laparoscopic partial nephrectomy. J Urol. 2011;186: 53-58. 16. Becker F, Van Poppel H, Hakenberg OW, et al. Assessing the impact of ischaemia time during partial nephrectomy. Eur Urol. 2009;56:625-634. 17. Thompson RH, Lane BR, Lohse CM, et al. Every minute counts when the renal hilum is clamped during partial nephrectomy. Eur Urol. 2010;58:340-345. 18. Simmons MN, Schreiber MJ, Gill IS. Surgical renal ischemia: a contemporary overview. J Urol. 2008;180:19-30. 19. Kaul S, Laungani R, Sarle R, et al. da Vinci- assisted robotic partial nephrectomy: technique and results at a mean of 15 months of follow-up. Eur Urol. 2007;51:186-192. 20. Caruso RP, Phillips CK, Kau E, et al. Robot assisted laparoscopic partial nephrectomy: initial experience. J Urol. 2006;176:36-39. 21. Benway BM, Bhayani SB, Rogers CG, et al. Robot-assisted partial nephrectomy: an international experience. Eur Urol. 2010;57: 815-820. 22. Breda A, Stepanian SV, Liao J, et al. Positive margins in laparoscopic partial nephrectomy in 855 cases: a multi-institutional survey from the United States and Europe. J Urol. 2007;178:47-50. 23. Yossepowitch O, Thompson RH, Leibovich BC, et al. Positive surgical margins at partial nephrectomy: predictors and oncological outcomes. J Urol. 2008;179:2158-2163. 24. Bensalah K, Pantuck AJ, Rioux-Leclercq N, et al. Positive surgical margin appears to have negligible impact on survival of renal cell carcinomas treated by nephron-sparing surgery. Eur Urol. 2010;57: 466-473. 25. Lerner SE, Hawkins CA, Blute ML, et al. Disease outcome in patients with low stage renal cell carcinoma treated with nephron sparing or radical surgery. J Urol. 1996;155:1868-1873. 26. Hafez KS, Fergany AF, Novick AC. Nephron sparing surgery for localised renal cell carcinoma: impact of tumour size on patient survival, tumour recurrence and TNM staging. J Urol. 1999;162: 1930-1933. 27. Lane BR, Gill IS. 5-Year outcomes of laparoscopic partial nephrectomy. J Urol. 2007;177:70-74. 28. Naeem N, Petros F, Sukumar S, et al. Robot-assisted partial nephrectomy in obese patients. J Endourol. 2011;25:101-105. 29. Autorino R, Cadeddu JA, Desai MM, et al. Laparoendoscopic single-site and natural orifice transluminal endoscopic surgery in urology: a critical analysis of the literature. Eur Urol. 2011;59: 26-45. 30. Khanna R, White MA, Autorino R, et al. Selection of a port for use in laparoendoscopic single-site surgery. Curr Urol Rep. 2011;12: 94-99.
599
RESULTS
CONCLUSION
To assess the functional and oncologic outcomes of robotic laparoendoscopic single site surgery (LESS) partial nephrectomy with a minimum of 2-year follow-up. Thirty-nine consecutive patients who had undergone robotic LESS partial nephrectomy were identified with a minimum of 2-year follow-up. Perioperative data were recorded along with functional and oncologic outcomes. Patient’s estimated glomerular filtration rate was determined using the Modification of Diet in Renal Disease formula. A univariate analysis was performed using independent samples t test. Data are presented as medians with interquartile range and counts or frequencies with percentages or proportion. The median age was 51 (45, 59). The median resected tumor size was 3 cm (2, 3.7), and the median operative time was 185 minutes (135, 237). The median estimated blood loss was 150 mL (70, 150), and the median warm ischemia time was 25 minutes (17, 35). The estimated glomerular filtration rate did not change significantly at 24 month follow-up with a mean decrease of 6.4 mL/minute/1.73 m2 (7.5%, P ¼ .22). Renal cell carcinoma was confirmed in 33 patients (85%) with tumor stage pT1a in 26 patients (78%). There was 1 patient with a positive surgical margin. At a median follow-up of 26 months (24, 32), there was no local recurrence and only 1 distant recurrence was detected. This study appears to be the first to report on intermediate term functional and oncologic outcomes after robotic LESS partial nephrectomy. It has shown comparable results with other minimal invasive surgical options. UROLOGY 82: 595e599, 2013. 2013 Elsevier Inc.
N
ephron sparing surgery is now considered as the standard treatment for small renal tumors whenever it is technically feasible, owing to the advantage of preserving renal function and with long-term oncologic results equivalent to that of radical nephrectomy.1 Laparoscopic partial nephrectomy has emerged as a viable alternative to open partial nephrectomy for clinical stage T1 renal tumor, with similar oncologic and functional outcomes and also convalescence benefits.2 Since the first laparoscopic nephrectomy reported by Clayman et al in 1990, there have been major breakthroughs in laparoscopic surgery of the urinary tract.3 Financial Disclosure: The authors declare that they have no relevant financial interests. Funding Support: This study was supported by a faculty research grant of Yonsei University College of Medicine for 2012 (6-2012-0181). From the Urological Society of Australia and New Zealand, Edgecliff, New South Wales, Australia; the Department of Urology, University of Miami, Miller School of Medicine, Miami, FL; and the Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea Reprint requests: Koon H. Rha, M.D., Ph.D., Department of Urology, Urological Science Institute, Yonsei University College of Medicine, 250 Seongsanno, Seodaemungu, Seoul 120-752, Republic of Korea. E-mail: [email protected] Submitted: January 23, 2013, accepted (with revisions): May 5, 2013
ª 2013 Elsevier Inc. All Rights Reserved
With technological advancements and improvements in equipment, urologists have gained significant momentum in further minimizing the surgical approach with the development of laparoendoscopic single site surgery (LESS). LESS involves accessing the abdominal cavity through a readily concealed 3 cm-4 cm incision at the umbilicus, hence might minimize patient discomfort, shorten convalescence, and improve cosmesis.4 However, challenges encountered with LESS include difficulty with using the novel bent and articulating instruments in close proximity to one another, resulting in loss of triangulation and instrument clashing.5 The introduction of robotic technology has provided some attractive features such as magnified 3 dimensional vision, articulating instruments, scaling of movement and tremor filtration, fourth robotic arm assistance, and TilePro, a live intraoperative ultrasound platform. Consequently, these features have reduced the crowding of instruments, enabled better precision with tumor resection and renal reconstruction. Nevertheless, there is still paucity of relevant studies of robotic LESS partial nephrectomy on its intermediate term clinical outcomes as it is a relatively new approach. 0090-4295/13/$36.00 http://dx.doi.org/10.1016/j.urology.2013.05.010
595
In this study, we analyzed the 2-year functional and oncologic outcomes of robotic LESS partial nephrectomy using a homemade single-port device.
MATERIALS AND METHODS Forty-four consecutive patients who had undergone robotic LESS partial nephrectomy were identified initially from our institutional review board approved computerized database between May 2009 and March 2010. Five patients who had other concurrent procedures performed were excluded. The remaining 39 patients who had a minimum of 2 years follow-up were analyzed. Our operative technique of robotic LESS partial nephrectomy using homemade single port device has been detailed previously.6 The patient was placed in the conventional flank position at approximately 45 with the ipsilateral side elevated. A 4-cm-long incision was made down to the peritoneum over the umbilicus, followed by installment of an Alexis wound retractor (Applied Medical, Rancho Santa Margarita, CA). A size 7 surgical glove was then applied over the external side of the Alexis wound retractor and a homemade single port was established by inserting two 12-mm trocars and two 8-mm trocars through the fingers of a surgical glove and securing it to the port (Fig. 1A). The camera was inserted through the 12-mm port of the homemade single port, the robot arms were inserted through the 8-mm robotic port, and the second 12-mm port was used for insufflation and as an assistant port. The fourth robotic arm is not routinely used in our patients. For right-sided cases, an addition 5-mm port is inserted in the subxiphoid area for liver retraction. The robot was then docked over the patient’s shoulder, with the camera oriented in line with the kidney (Fig. 1B). The specimen is retrieved in the 10 mm endocatch bag and removed through the umbilical single port site. All the patients in the present study were completed with da Vinci S surgical system (Intuitive Surgical, Sunnyvale, CA). Intraoperative ultrasound with TilePro projection onto the console screen was used to confirm the margins of the mass and guide scoring the renal capsule with electrocautery. Temporary occlusion of the renal artery and vein was performed by the placement of laparoscopic bulldog clamps by the assistant. The tumor was then excised using the Endowrist monopolar scissors (Intuitive Surgical, Sunnyvale, CA). Frozen section biopsy specimens of the tumor base were taken. The renal defect was reconstructed using the sliding clip technique. At our institution, patient routine follow-up consisted of history and physical examination, and serum creatinine at 1, 3, 6, and 12 months, and then annually thereafter. Radiographic evaluation comprised computerized tomography or magnetic resonance imaging of the chest and abdomen at 6 months, and then annually after robotic LESS partial nephrectomy. Nephrometry score was used to characterize the renal tumor anatomy by using the R.E.N.A.L system (Radius; exophytic or endophytic, nearness to the renal sinus fat or collecting system, anterior or posterior position, and location).7 Patient’s estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Disease formula.8 Complications were graded according to the Clavien classification.9
Statistical Analysis A univariate analysis was performed using independent samples t test. Data were presented as medians with interquartile range
596
Figure 1. (A) Schematic drawing of homemade device with ports inserted into the digits of the surgical glove. (B) Schematic drawing of the homemade device after docking of robot, with the assistant port shown in black arrow. (Color version available online.) and counts or frequencies were expressed as percentages. All statistical analyses were performed using the SPSS software package (IBM Corp., Somers, NY) and a P value <.05 was considered statistical significant.
RESULTS Thirty-nine consecutive patients with a minimum of 2 years follow-up were available for evaluation. There were 15 patients with right-sided renal tumor and 24 patients with left-sided renal tumor. All patients were completed with a homemade single port device except for 1 patient who was converted to mini incision partial nephrectomy owing to difficulty in accessing the endophytic tumor located at the right posterior upper pole with the robotic arm. Demographic data are outlined in Table 1. The median age of patient was 51 (45, 59), with 25 men and 14 women, respectively. The overall mean and median nephrometry scores were 6.7 and 7, respectively (range 4-11; interquartile range 6, 8). The clinical results are summarized in Table 2. The median operative time was 185 minutes (135, 237), with median warm ischemia time of 25 minutes (17, 35). The median estimated blood loss was 150 mL (70, 150), and the median
UROLOGY 82 (3), 2013
Table 1. Demographic data
Table 2. Clinical results
Median age (IQR) 51 (45, 59) Sex, male 25 Median BMI (IQR) 23.2 (21.9, 25.2) Comorbidities Diabetes 3 (7%) Hypertension 9 (23%) ASA 1 and 2 37 (95%) 3 and 4 2 (5%) Median tumor size, cm (IQR) 3 (2, 3.7) Mean/median nephrometry 6.7/7 (6, 8) score (IQR) Low (4 to 6) 14 (36%) Moderate (7 to 9) 20 (51%) High (10 to 12) 5 (13%) Nephrometry score components R-score (maximal diameter, cm) 4 (1 point) 29 >4 but <7 (2 points) 9 7 (3 points) 1 E-score (exophicity) 50% (1 point) 25 50% (2 points) 14 Entirely endophytic (3 points) 0 N-score (nearness of tumor to sinus mm) 7 (1 point) 4 >4 but <7 (2 points) 30 4 (3 points) 5 A/P designation (anterior vs posterior) Anterior 26 Posterior 13 L-score (polar line location) Entirely above upper or below 5 lower polar line (1 point) Tumor crosses polar line 28 (2 points) >50% of tumor cross polar line 6 or is entirely within the polar lines (3 points)
Median operative time, min (IQR) Median warm ischemia time, min (IQR) Median estimated blood loss, mL (IQR) Conversion to open partial nephrectomy Histology subtypes Conventional RCC Other RCC subtype Benign Positive final margin Pathologic stage pT1a pT1b pT2 or higher Median baseline GFR, mL/min/ 1.73 m2 (IQR) Median GFR at 1 mo, mL/min/ 1.73 m2 (IQR) Median GFR at 3 mo, mL/min/ 1.73 m2 (IQR) Median GFR at 6 mo, mL/min/ 1.73 m2 (IQR) Median GFR at 12 mo, mL/min/ 1.73 m2 (IQR) Mean GFR at 24 mo, mL/min/ 1.73 m2 (IQR) % Change mean GFR at 24 mo Median follow-up, mo (IQR) Complications Grade 2 (hemorrhage requiring transfusion) Grade 3 (urine leak requiring stent)
ASA, American Society of Anesthesiologists; BMI, body mass index; IQR, interquartile range.
resected tumor size was 3 cm (2, 3.7). The final histologic analysis showed renal cell carcinoma in 33 patients (85%), of which, 26 patients (79%) had Fuhrman grade I/II. There were 26 patients (79%) with pathologic stage pT1a, 6 patients (18%) with pT1b, and 1 patient (3%) with pT2. All surgical margins were pathologically negative except for 1 patient, with a positive margin rate of 3%. All patients except for 2 reported a preoperative eGFR of more than 60 mL/minute/1.73 m2. The eGFR did not change significantly at the 24 month follow-up with a mean decrease of 6.4 mL/minute/1.73 m2 (7.5%, P ¼ .22). The median follow-up was 26 months (24, 32) and no patients required dialysis. There were 2 intraoperative complications; 1 patient had renal vein injury, which was successfully controlled with intracorporeal suturing, whereas the other patient had ureteric injury and required insertion of a ureteric stent. Postoperative complications occurred in 6 patients (15%), of which 5 required blood transfusion (DindoClavien grade 2) and 1 patient developed urine leakage UROLOGY 82 (3), 2013
185 (135, 237) 25 (17, 35) 150 (70, 150) 1 (2.5%) 28 5 6 1 26 6 1 85.4
(72%) (13%) (15%) (3%) (79%) (18%) (3%) (77.7, 98.1)
78 (68.7, 90) 74.6 (68.2, 88) 75.6 (68.8, 88) 78 (70.3, 89) 79 (71, 90) 7.5% (P ¼ .22) 26 (24, 32) 5 (13%) 1 (2.5%)
GFR, glomerular filtration rate; RCC, renal cell carcinoma; other abbreviation as in Table 1.
(Dindo-Clavien grade 3), which was managed with a ureteric stent. There was only 1 patient (3%) with distant pulmonary metastasis at 18 months who had a high-grade pT1b papillary renal cell carcinoma with negative margin. There were no patients who experienced local recurrence, death from cancer, or other causes.
COMMENT Urology has increasingly become a technology-driven specialty, where minimal invasive surgery is now part of the standard armory. Robotic LESS partial nephrectomy represents an attractive and minimally invasive treatment option for patients with small renal tumors. Our initial experiences with conventional LESS and robotic LESS in urology were reported in collaboration with the largest worldwide multi-institutional study.10 To our knowledge, the present study is the first that directly assesses the intermediate term functional and oncologic outcomes of robotic LESS partial nephrectomy. Analyzing the renal function outcomes, the eGFR did not change significantly at the follow-up of 24 months with a mean decrease of 6.4 mL/minute/1.73 m2 (7.5%, P ¼ .22) and is within 597
Table 3. Oncologic outcomes of selected series of partial nephrectomy for renal masses Study Lerner et al25 Hafez et al26 Gill et al2 Gill et al2 Lane and Gill27 Benway et al21 Present study
Approach
Patient No.
Median Follow-up (mo)
Median Tumor Size (cm)
Local Recurrence %
Distant Recurrence %
Open Open Open Laparoscopic Laparoscopic Robotic Robotic LESS
185 485 1029 771 58 183 39
44 (Mean) 47 (Mean) 34 15 68 16 26
4.1 2.7 3.5 2.9 2.9 2.87 3
5.9 3.2 1.5 2.7 2.7 0 0
17 5.8 2.1 0.9 0 0 3
LESS, laparoendoscopic single site surgery.
the range (4.5-8.0 mL/minute/1.73 m2) of those reported series.11-14 The mean GFR decrease was the greatest at 3 months and then recovered progressively toward the preoperative level. Detailed description of eGFR changes over time is reported in Table 2. Song et al have shown that the recovery of renal function after partial nephrectomy is impacted by patient age, comorbidities, and baseline renal function, along with the amount and depth of parenchyma excised.15 Interestingly, these investigators have reported warm ischemia times to have no impact on renal function. One possible explanation for this observation in the aforementioned study is that fewer patients had baseline compromise (ie pre-existing comorbidities and chronic kidney disease). Nevertheless, a large body of published data has shown that warm ischemia time is a significant predictor of ultimate renal function.16-18 Our median warm ischemia time of 25 minutes is comparable with other published robotic series ranging from 21 to 31 minutes.13,19,20 One patient had a positive surgical margin, despite the fact that the intraoperative frozen section of the resection margin was negative. This 62-year-old woman had a 2.2 cm Fuhrman 3 clear cell renal cell carcinoma. Her subsequent follow-up serial radiological studies have ruled out any evidence of local or distant recurrence. Our positive surgical margin rate of 3% is consistent with previous robotic and laparoscopic series.21,22 In a retrospective study, Benway et al reported a positive margin rate of 2.7% of the 183 patients who underwent robotic partial nephrectomy at 4 centers.21 Likewise, in a multiinstitutional survey of 17 academic centers in the United States and Europe, there were 21 identified cases of positive surgical margins in an overall series of 855 laparoscopic partial nephrectomy (2.4%).22 Moreover, the presence of positive resection margin has been shown to have no adverse effect on the overall oncologic outcome. A large study by 2 institutions in the United States had shown that positive surgical margins in partial nephrectomy specimens do not appear to increase the long-term risk of local recurrence or metastatic progression, and that patients with a positive surgical margin can be monitored closely without compromising on long-term disease-free survival.23 Another multi-institutional European retrospective study had revealed that the indication and tumor location, rather than margin status, were
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significant predictors of local recurrence with a mean follow-up of 37 months.24 No single local recurrence was detected in the present study; however, 1 patient developed pulmonary metastasis at 18 months follow-up. This was a 74-year-old man who had a 4.3 cm papillary type renal cell carcinoma with negative resection margin. He was referred to a medical oncologist and was commenced on sorafenib treatment (tyrosine kinase inhibitor) for his metastatic renal cell carcinoma. He was due to have subsequent radiographic imaging after the treatment course. Our 0% local recurrence and 3% distal recurrence rates are comparable with some of the major series in the published reports listed in Table 3. There was no patient from the present study who died from cancer specific or other causes. It is noteworthy that the cohort in this study was generally not obese with a mean body mass index of 23.2 (21.9, 25.2). As such, the result from this study might not be extrapolated into other countries where obesity is an issue. It is well established that obese patients are more likely to have multiple medical comorbidities, including hypertension and diabetes. Naeem et al had recently reported that robotic partial nephrectomy in obese patients resulted in higher estimated blood loss and a trend toward greater operative time and warm ischemia time.28 We recognize some of the limitations in the present study. The main one is the retrospective nature of the analysis, albeit our data were collected prospectively into a computerized database. Another limitation is the relatively small sample size. It is likely that larger prospective comparative studies will appear as experience with this new and emerging technique increases in the future and the learning curve is overcome. Furthermore, the use of an additional 5-mm subxiphoid liver retraction port for right-sided renal tumors was a deviation of the strict philosophy of LESS surgery; however, this seems to have become an accepted practice.29 Nevertheless, it must be acknowledged that the main disadvantage with our current technique is the fragility of the homemade single port access device, where accidental laceration of the glove during insertion of robotic instruments could have caused air leakage. There was 1 patient who required port-glove replacement because of ongoing air leak intraoperatively. Although several commercially
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available single port access devices have been reported in published reports, it is inevitable that more research is required for the development and design of an ideal robotic platform.30
CONCLUSION This study appears to be the first to report on functional and oncologic outcomes after robotic LESS partial nephrectomy in the intermediate term. It has shown comparable results with other minimal invasive surgical options for the management of renal parenchymal tumor. However, there is potential in the future for longer term follow-up analysis, extending to larger study size across multi-institutions. Finally significant improvements are required to address the current challenge of robotic LESS surgery before this technique might be considered as the standard of care. References 1. Campbell SC, Novick AC, Belldegrun A, et al. Guideline for management of the clinical T1 renal mass. J Urol. 2009;182: 1271-1279. 2. Gill IS, Kavoussi LR, Lane BR, et al. Comparison of 1,800 laparoscopic and open partial nephrectomies for single renal tumors. J Urol. 2007;178:41-46. 3. Clayman RV, Kavoussi LR, Soper NJ, et al. Laparoscopic nephrectomy: initial case report. J Urol. 1991;146:278-282. 4. Gettman MT, Box G, Averch T, et al. Concensus statement on natural orifice transluminal endoscopic surgery and single-incision laparoscopic surgery: heralding a new era in urology? Eur Urol. 2008;53:1117-1120. 5. Autorino R, Kaouk JH, Stolzenburg JU, et al. Current status and future directions of robotic single-site surgery: a systematic review. Eur Urol. 2013;63:266-280. 6. Jeon HG, Jeong W, Oh CK, et al. Initial experience with 50 laparoendoscopic single site surgeries using a homemade, single port device at a single center. J Urol. 2010;183:1866-1871. 7. Kutikov A, Uzzo RG. The R.E.N.A.L. nephrometry score: a comprehensive standardized system for quantitating renal tumor size, location and depth. J Urol. 2009;182:844-853. 8. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461-470. 9. Dindo D, Demartines N, Clavien PA. Classification of surgical complications. Ann Surg. 2004;240:205-213. 10. Kaouk JH, Autorino R, Kim FJ, et al. Laparoendocopic single-site surgery in urology: worldwide multi-institutional analysis of 1076 cases. Eur Urol. 2011;60:998-1005. 11. Rogers CG, Singh A, Blatt AM, et al. Robotic partial nephrectomy for renal hilar tumours: a multiinstitutional analysis. J Urol. 2008; 180:2353-2356.
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12. Gong Y, Du C, Josephson DY, et al. Four-arm robotic partial nephrectomy for complex renal cell carcinoma. World J Urol. 2010; 28:111-115. 13. Rogers CG, Singh A, Blatt AM, et al. Robotic partial nephrectomy for complex renal tumours: surgical technique. Eur Urol. 2008;53: 514-523. 14. Scoll BJ, Uzzo RG, Chen D, et al. Robot-assisted partial nephrectomy: a large single-institutional experience. Urology. 2010;75: 1328-1334. 15. Song C, Park S, Jeong IG, et al. Followup of unilateral renal function after laparoscopic partial nephrectomy. J Urol. 2011;186: 53-58. 16. Becker F, Van Poppel H, Hakenberg OW, et al. Assessing the impact of ischaemia time during partial nephrectomy. Eur Urol. 2009;56:625-634. 17. Thompson RH, Lane BR, Lohse CM, et al. Every minute counts when the renal hilum is clamped during partial nephrectomy. Eur Urol. 2010;58:340-345. 18. Simmons MN, Schreiber MJ, Gill IS. Surgical renal ischemia: a contemporary overview. J Urol. 2008;180:19-30. 19. Kaul S, Laungani R, Sarle R, et al. da Vinci- assisted robotic partial nephrectomy: technique and results at a mean of 15 months of follow-up. Eur Urol. 2007;51:186-192. 20. Caruso RP, Phillips CK, Kau E, et al. Robot assisted laparoscopic partial nephrectomy: initial experience. J Urol. 2006;176:36-39. 21. Benway BM, Bhayani SB, Rogers CG, et al. Robot-assisted partial nephrectomy: an international experience. Eur Urol. 2010;57: 815-820. 22. Breda A, Stepanian SV, Liao J, et al. Positive margins in laparoscopic partial nephrectomy in 855 cases: a multi-institutional survey from the United States and Europe. J Urol. 2007;178:47-50. 23. Yossepowitch O, Thompson RH, Leibovich BC, et al. Positive surgical margins at partial nephrectomy: predictors and oncological outcomes. J Urol. 2008;179:2158-2163. 24. Bensalah K, Pantuck AJ, Rioux-Leclercq N, et al. Positive surgical margin appears to have negligible impact on survival of renal cell carcinomas treated by nephron-sparing surgery. Eur Urol. 2010;57: 466-473. 25. Lerner SE, Hawkins CA, Blute ML, et al. Disease outcome in patients with low stage renal cell carcinoma treated with nephron sparing or radical surgery. J Urol. 1996;155:1868-1873. 26. Hafez KS, Fergany AF, Novick AC. Nephron sparing surgery for localised renal cell carcinoma: impact of tumour size on patient survival, tumour recurrence and TNM staging. J Urol. 1999;162: 1930-1933. 27. Lane BR, Gill IS. 5-Year outcomes of laparoscopic partial nephrectomy. J Urol. 2007;177:70-74. 28. Naeem N, Petros F, Sukumar S, et al. Robot-assisted partial nephrectomy in obese patients. J Endourol. 2011;25:101-105. 29. Autorino R, Cadeddu JA, Desai MM, et al. Laparoendoscopic single-site and natural orifice transluminal endoscopic surgery in urology: a critical analysis of the literature. Eur Urol. 2011;59: 26-45. 30. Khanna R, White MA, Autorino R, et al. Selection of a port for use in laparoendoscopic single-site surgery. Curr Urol Rep. 2011;12: 94-99.
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